KEIO RESEARCHERS INFORMATION SYSTEM

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• 医学博士, The University of Tokyo, Dissertation, 2006.06

  BrmとBRG1の発現を共に欠失するヒト非小細胞肺がん細胞株における神経特異的遺伝子群の発現誘導とその機構

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Neuroscience-general

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• Ａｌｚｈｅｉｍｅｒ’ｓ　ｄｉｓｅａｓｅ

• synapse

Research Themes 【 Display / hide 】

Research Themes 【 Display / hide 】

• Analysis of Alzheimer-related molecules in the synapse, 

  2017.04

  -

  2020.03

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Pathological Progression Induced by the Frontotemporal Dementia-Associated R406W Tau Mutation in Patient-Derived iPSCs

  Nakamura M., Shiozawa S., Tsuboi D., Amano M., Watanabe H., Maeda S., Kimura T., Yoshimatsu S., Kisa F., Karch C., Miyasaka T., Takashima A., Sahara N., Hisanaga S., Ikeuchi T., Kaibuchi K., Okano H.

  Stem Cell Reports （Stem Cell Reports)  13 （ 4 ） 684 - 699 2019.10

  ISSN  22136711

  　View Summary

  © 2019 The Author(s) Mutations in the microtubule-associated protein tau (MAPT) gene are known to cause familial frontotemporal dementia (FTD). The R406W tau mutation is a unique missense mutation whose patients have been reported to exhibit Alzheimer's disease (AD)-like phenotypes rather than the more typical FTD phenotypes. In this study, we established patient-derived induced pluripotent stem cell (iPSC) models to investigate the disease pathology induced by the R406W mutation. We generated iPSCs from patients and established isogenic lines using CRISPR/Cas9. The iPSCs were induced into cerebral organoids, which were dissociated into cortical neurons with high purity. In this neuronal culture, the mutant tau protein exhibited reduced phosphorylation levels and was increasingly fragmented by calpain. Furthermore, the mutant tau protein was mislocalized and the axons of the patient-derived neurons displayed morphological and functional abnormalities, which were rescued by microtubule stabilization. The findings of our study provide mechanistic insight into tau pathology and a potential for therapeutic intervention.

  • Access to Document (DOI)

• A combinational treatment of carotenoids decreases Aβ secretion in human neurons via β-secretase inhibition

  Sho M., Ichiyanagi N., Imaizumi K., Ishikawa M., Morimoto S., Watanabe H., Okano H.

  Neuroscience Research （Neuroscience Research)   2019

  ISSN  01680102

  　View Summary

  © 2019 Alzheimer's disease (AD) is the most common cause of dementia and is characterized neuropathologically by the presence of amyloid plaques and neurofibrillary tangles. Amyloid-β (Aβ) peptides, major components of amyloid plaques and crucial pathogenic molecules in terms of the amyloid hypothesis, are derived from successive proteolytic processing of amyloid-β precursor protein (APP). In this study, we established a human neuronal culture system using induced pluripotent stem cells (iPSCs) to evaluate the possible effects of natural compounds on the amyloid phenotype. Unexpectedly, we found that combinational treatment of carotenoids, but not docosahexaenoic acid, significantly decreased Aβ secretion from iPSC-derived human cortical neurons. Importantly, the effects of the carotenoids resulted from specific inhibition of BACE1 activity and not from expression changes in APP or BACE1. Therefore, these results indicate a novel beneficial function of carotenoids in the anti-amyloidogenic processing of APP. Collectively, this study will shed light on neuronal protection by a novel mechanism during the pathogenesis of AD.

  • Access to Document (DOI)

• Reconsidering Animal Models of Major Depressive Disorder in the Elderly

  Toda, Shigenobu, Iguchi, Yoshio, Lin, Ziqiao, Nishikawa, Hiromi, Nagasawa, Tatsuya, Watanabe, Hirotaka, Minabe, Yoshio

  FRONTIERS IN AGING NEUROSCIENCE 8   10727 - 10735 2016.08

  Research paper (scientific journal),  ISSN  1663-4365

  • Access to Document (DOI)

• Presenilin-1 Knockin Mice Reveal Loss-of-Function Mechanism for Familial Alzheimer's Disease

  Xia, Dan, Watanabe, Hirotaka, Wu, Bei, Lee, Sang Hun, Li, Yan, Tsvetkov, Evgeny, Bolshakov, Vadim Y., Shen, Jie, Kelleher, Raymond J., III

  NEURON 85 （ 5 ） 967 - 981 2015.03

  Research paper (scientific journal),  ISSN  0896-6273

  • Access to Document (DOI)

• Partial Loss of Presenilin Impairs Age-Dependent Neuronal Survival in the Cerebral Cortex

  Watanabe, Hirotaka, Iqbal, Minah, Zheng, Jin, Wines-Samuelson, Mary, Shen, Jie

  JOURNAL OF NEUROSCIENCE 34 （ 48 ） 15912 - 15922 2014.11

  Research paper (scientific journal),  ISSN  0270-6474

  • Access to Document (DOI)

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Papers, etc., Registered in KOARA 【 Display / hide 】

Papers, etc., Registered in KOARA 【 Display / hide 】

• Study of synaptic mechanism for Alzheimer's disease pathogenesis

  Watanabe, Hirotaka

  科学研究費補助金研究成果報告書 2019

• Development of neuron-specific analytical method to elucidate the mechanism underlying AD pathogenesis

  Watanabe, Hirotaka

  科学研究費補助金研究成果報告書 2016

Research Projects of Competitive Funds, etc. 【 Display / hide 】

Research Projects of Competitive Funds, etc. 【 Display / hide 】

• シナプス活動変容からアプローチするアルツハイマー病発症機序の解明

  2022.04

  -

  2026.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, 基盤研究(B), Principal investigator

• ミクログリア機能変容に着目したアルツハイマー病モデルの開発

  2021.09

  -

  2023.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, 学術変革領域研究(A), Principal investigator

• プレシナプスにおけるアルツハイマー病発症の分子機序解析

  2017.04

  -

  2020.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

• Development of neuron-specific analytical method to elucidate the mechanism underlying AD pathogenesis

  2015.08

  -

  2017.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Research Activity Start-up , Principal investigator

  　View Summary

  In this research proposal, I aimed to isolate single neuron from entorhinal cortex layer 2/3 of adult mouse, which is most likely vulnerable neuronal population in Alzheimer’s disease patients. First, I dissected out entorhinal cortex layer 2/3 from mouse brain slice under stereoscopic microscope, followed by trypsin treatment. Next, I picked single neurons with micropipette, and cDNAs fom each single neuron were synthesized for RT-PCR analysis. Several marker genes specific for entorhinal cortex layer 2/3 can be successfully detected by semiquantitative RT-PCR.

Intellectual Property Rights, etc. 【 Display / hide 】

Intellectual Property Rights, etc. 【 Display / hide 】

• Novel Receptor Polypeptides and Polynucleotides Encoding the Same.

  Date applied： PCT/JP2003/003050  2003.03 

  Patent, Joint

• A Novel Method for Constructing Gene-Targeting Vectors.

  Date applied： P2000-81795  2000.03 

  Patent, Joint

Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• PHYSIOLOGY 2

  2024

• PHYSIOLOGY 2

  2023

• PHYSIOLOGY 2

  2022

• PHYSIOLOGY 2

  2021

• PHYSIOLOGY 2

  2020

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Memberships in Academic Societies 【 Display / hide 】

Memberships in Academic Societies 【 Display / hide 】

• Society for Neuroscience, 

  2010.05

  -

  Present

• The Japan Neuroscience Society, 

  2006.11

  -

  Present